FOXO4-DRI
Also known as: FOX04-DRI, FOXO4 D-Retro-Inverso, Proxofim
Buy in shop
FOXO4-DRI from $318/kit
3 verified vendors, ≥99% purity, COAs included.
Key Facts: FOXO4-DRI
- Category
- Anti-Aging
- FDA Status
- Not FDA Approved
- Clinical Status
- Preclinical - Extensive animal research, no human trials initiated yet
- Administration
- Subcutaneous injection (community), IV/IP in animal studies
- Typical Dose
- 2-10 mg every other day for 3 doses (one cycle)
- Frequency
- 3 doses every other day, 1-3 cycles per year
- Duration
- 1 cycle = 3 doses over 5-6 days, repeat 1-3x yearly
Mechanism of Action
Senescent cells should die but don't, partly because the protein FOXO4 holds p53 hostage in the nucleus, keeping the cell's self-destruct program switched off. FOXO4-DRI is a peptide based on a FOXO4 sequence that competes for that interaction, freeing p53 and pushing it out of the nucleus, which triggers p53/p21-dependent apoptosis selectively in senescent cells. The 'DRI' stands for D-retro-inverso: the peptide is built from D-amino acids in reversed order, a design that resists enzyme breakdown and improves stability while preserving the binding shape. The selectivity is the appeal, since healthy proliferating cells are largely spared in the preclinical work.
Research Summary
The foundational study (Baar et al., Cell, 2017) reported that FOXO4-DRI selectively pushed senescent cells into apoptosis and, in mice, restored fur density, kidney function, and physical fitness, and helped counteract the toxicity of the chemotherapy drug doxorubicin. That is a striking result and it kicked off real interest in senolytic peptides. A few honest caveats. Some vendor and blog claims, like a specific percent lifespan extension, are not supported by the original paper and appear fabricated. Independent groups have since shown FOXO4-DRI can clear senescent human cells in culture (for example, expanded chondrocytes), and newer peptides report being several-fold more potent. Bottom line: the mouse and in vitro data are interesting, but there are no published human clinical trials, no established safe human dose, and long-term safety is unknown.
Dosing Information
Note: Animal study doses may not translate directly to humans.
Typical Dosingⓘ
Community experience
2-10 mg every other day for 3 doses (one cycle)
2-25 mg per injection, 6-75 mg total per cycle
3 doses every other day, 1-3 cycles per year
Senolytic peptide - used in short intermittent cycles, not daily. Mouse studies used 5 mg/kg x3 doses (translates to ~25 mg/dose for 60kg human). Biohacker protocols vary: some use 2-3 mg every other day for 6 days, others use higher 10-25 mg doses for 3 injections. Lower-dose protocols (300-500 mcg daily for weeks) also reported. Subcutaneous injection most common. Side effects may include injection site reactions, fatigue, muscle soreness, nausea.
Research Dosingⓘ
Scientific studies
Doses from animal studies and biohacker community protocols
Doses from Studies
5 mg/kg in mice x3 doses
Preclinical Research - Cell 2017 - Restoration of tissue homeostasis ↗
2-3 mg every other day for 6 days
Community Protocol - Biohacker protocols (Ben Greenfield et al.) ↗
Duration
1 cycle = 3 doses over 5-6 days, repeat 1-3x yearly
Administration
Subcutaneous injection (community), IV/IP in animal studies
Timing & Administration
Best Time to Take
Per research protocol
Intermittent dosing (e.g., 3 doses over 1 week, then break)
Food Recommendation
With or without food
Why This Timing?
FOXO4-DRI is typically administered in intermittent treatment cycles rather than daily dosing. The peptide triggers apoptosis in senescent cells, which then need time for clearance and tissue regeneration.
Possible Side Effects
Not everyone experiences these effects. Individual responses vary based on dosage, duration, and personal factors.
- ●Generally well-tolerated in animal studies
- ●Injection site reactions (burning, itching)
- ●Fatigue
- ●Muscle soreness
- ●Nausea
- ●No significant effects on platelet levels or blood values in animal studies
- ●No observed damage to non-proliferative tissues (heart)
- ●Limited human safety data
- ●Theoretical concern: could affect beneficial senescent cells (wound healing, tumor suppression)
References
- https://pmc.ncbi.nlm.nih.gov/articles/PMC8601985/
- https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2021.677576/full
- https://www.nature.com/articles/nrd.2017.98
Research This Peptide Further
Buy in shop
FOXO4-DRI from $318/kit
3 verified vendors, ≥99% purity, COAs included.
Frequently Asked Questions
What does FOXO4-DRI do?
FOXO4-DRI is an experimental senolytic peptide, meaning it is designed to kill off worn-out 'zombie' cells (senescent cells) while leaving healthy ones alone. It comes from a single influential 2017 mouse study and is engineered with a clever stability trick. It has never been tested in a human clinical trial, so anything beyond 'promising in mice' is speculation.
How does FOXO4-DRI work?
Senescent cells should die but don't, partly because the protein FOXO4 holds p53 hostage in the nucleus, keeping the cell's self-destruct program switched off. FOXO4-DRI is a peptide based on a FOXO4 sequence that competes for that interaction, freeing p53 and pushing it out of the nucleus, which triggers p53/p21-dependent apoptosis selectively in senescent cells. The 'DRI' stands for D-retro-inverso: the peptide is built from D-amino acids in reversed order, a design that resists enzyme breakdown and improves stability while preserving the binding shape. The selectivity is the appeal, since healthy proliferating cells are largely spared in the preclinical work.
Is FOXO4-DRI FDA approved?
No, FOXO4-DRI is not currently FDA approved. Current status: Preclinical - Extensive animal research, no human trials initiated yet
What are the side effects of FOXO4-DRI?
Reported side effects include: Generally well-tolerated in animal studies, Injection site reactions (burning, itching), Fatigue, Muscle soreness, Nausea. Individual responses vary based on dosage, duration, and personal health factors.
What is the typical dose of FOXO4-DRI?
Community-reported common dose: 2-10 mg every other day for 3 doses (one cycle) (3 doses every other day, 1-3 cycles per year). Range: 2-25 mg per injection, 6-75 mg total per cycle. Administration: Subcutaneous injection (community), IV/IP in animal studies. Community-reported doses from biohacker protocols. No human clinical trials completed. Not medical advice. Consult healthcare provider.
Related Peptides
Peptides commonly compared with FOXO4-DRI or used in similar applications.
Humanin
PreclinicalHumanin is a 24-amino-acid peptide encoded inside mitochondrial DNA (in the 16S rRNA gene), discovered in 2001 and named for its ability to protect human neurons from Alzheimer-related cell death. It was the first member of the mitochondrial-derived peptide family and is studied mainly for neuroprotection, cell survival, and metabolic and age-related disease. The honest status: it has the deepest preclinical evidence base of any mitochondrial peptide, but human therapeutic trials are essentially absent.
Anti-AgingVesilute
PreclinicalVesilute is marketed as a Khavinson-style short peptide bioregulator aimed at the urinary bladder and lower urinary tract. Vendor sources cannot even agree on its sequence: some list a Glu-Asp dipeptide, others a Lys-Glu-Asp tripeptide. There are no approvals and, importantly, no peer-reviewed studies published specifically on a peptide called Vesilute, so almost everything written about it is extrapolated from the broader bioregulator family rather than direct evidence.
Anti-AgingGlutathione
Clinical TrialsGlutathione is the body's main intracellular antioxidant, a tripeptide of glutamate, cysteine, and glycine (often written GSH). It is sold as oral, IV, topical, and inhaled products and marketed for everything from detox and immune support to skin lightening, but its real, evidence-backed role is as a redox buffer that neutralizes oxidative stress and supports liver detoxification. Some clinical evidence exists for specific uses, while many popular claims, especially IV skin whitening, rest on weak or risky data.
Anti-AgingDSIP
Clinical TrialsDSIP, or delta sleep-inducing peptide, is a small naturally occurring nonapeptide (sequence Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu) first isolated in the 1970s from the blood of sleeping rabbits. As the name suggests, it was named for its ability to promote delta-wave (deep, slow-wave) sleep in animals. Despite five decades of study it has no regulatory approval and the human evidence for it as a sleep aid is weak and inconsistent.
Anti-AgingNAD+ Precursors
Clinical TrialsNAD+ precursors are not peptides. They are small molecules, mainly nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), that the body converts into NAD+, a coenzyme every cell needs to make energy and run repair enzymes. NAD+ falls with age, so these precursors are sold as anti-aging and metabolic supplements. Human trials confirm they reliably raise blood NAD+ levels, but clear proof of real health benefits in people is still missing.
Anti-AgingSS-31
FDASS-31 (sequence D-Arg-Dmt-Lys-Phe-NH2), known generically as elamipretide and sold as FORZINITY, is a synthetic tetrapeptide that homes in on the energy-producing machinery inside your cells. It works by binding cardiolipin, a fat unique to the inner mitochondrial membrane, to help mitochondria run cleaner and make more ATP with less oxidative damage. This is the rare research peptide with a real regulatory finish line: the FDA granted it accelerated approval in September 2025 for Barth syndrome, though it has failed several other major trials.
Anti-AgingWant updates on FOXO4-DRI research?
Subscribe to get notified when we add new research findings, protocol updates, and related peptide information.